Several patients experienced tumor shrinkage of more than 80 percent within 12 weeks of receiving the drugs, and the shrinkage was long lasting. Further, 40 percent of patients who received varying concurrent dosages had an objective response — meaning at least a 50 percent reduction in tumor size. Side effects from the drug combination were manageable and often reversible.

Dr. Wolchok and his team combined ipilimumab and nivolumab because promising results in preclinical testing suggested the drugs impact the immune system in a complementary way. By blocking the inhibitory marker CTLA-4, ipilimumab, which the FDA approved for advanced melanoma in 2011, activates the immune system, prompting T cells to start attacking the tumor. Blocking PD-1 further activates T cells in a different manner, allowing them to continue the attack.

“Previous studies had shown that ipilimumab alone could prolong overall survival in advanced melanoma patients, and nivolumab alone could produce durable tumor responses in melanoma and other cancers, so the combination of the two drugs was quite logical and well supported by preclinical and clinical trial data,” he said.

However, Dr. Wolchok notes that not all patients respond to immunotherapy and determining why some patients do not is becoming an extremely important part of advancing this field.

Because of the strong Phase I findings, researchers will begin testing the combination this June as a therapy for patients newly diagnosed with advanced melanoma in a randomizedPhase III trial led by Memorial Sloan Kettering and taking place at more than 150 institutions worldwide.

The current research was supported by Bristol-Myers Squibb Inc and Ono Pharmaceutical Company Ltd.

Journalists may contact the Department of Public Affairs for more information.

antibody (AN-tee-BAH-dee)

A protein made by plasma cells (a type of white blood cell) in response to an antigen (a substance that causes the body to make a specific immune response). Each antibody can bind to only one specific antigen. The purpose of this binding is to help destroy the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

cancer (KAN-ser)

A term for diseases in which abnormal cells divide without control and can invade nearby tissues. Cancer cells can also spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is a cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is a cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is a cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord. Also called malignancy.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

clinical (KLIH-nih-kul)

Having to do with the examination and treatment of patients.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

drug (drug)

Any substance, other than food, that is used to prevent, diagnose, treat or relieve symptoms of a disease or abnormal condition. Also refers to a substance that alters mood or body function, or that can be habit-forming or addictive, especially a narcotic.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

FDA

An agency in the U.S. federal government whose mission is to protect public health by making sure that food, cosmetics, and nutritional supplements are safe to use and truthfully labeled. The FDA also makes sure that drugs, medical devices, and equipment are safe and effective, and that blood for transfusions and transplant tissue are safe. Also called Food and Drug Administration.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

IL

One of a group of related proteins made by leukocytes (white blood cells) and other cells in the body. ILs regulate immune responses. ILs made in the laboratory are used as biological response modifiers to boost the immune system in cancer therapy. An interleukin is a type of cytokine. Also called interleukin.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

immune system (ih-MYOON SIS-tem)

The complex group of organs and cells that defends the body against infections and other diseases.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

immunotherapy (IH-myoo-noh-THAYR-uh-pee)

Treatment to boost or restore the ability of the immune system to fight cancer, infections, and other diseases. Also used to lessen certain side effects that may be caused by some cancer treatments. Agents used in immunotherapy include monoclonal antibodies, growth factors, and vaccines. These agents may also have a direct antitumor effect. Also called biological response modifier therapy, biological therapy, biotherapy, and BRM therapy.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

investigational (in-VES-tih-GAY-shuh-nul)

In clinical trials, refers to a drug (including a new drug, dose, combination, or route of administration) or procedure that has undergone basic laboratory testing and received approval from the U.S. Food and Drug Administration (FDA) to be tested in human subjects. A drug or procedure may be approved by the FDA for use in one disease or condition, but be considered investigational in other diseases or conditions. Also called experimental.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

ipilimumab (ih-pih-LIH-myoo-mab)

A drug used to treat melanoma that has spread to other parts of the body or that cannot be removed by surgery. It is also being studied in the treatment of other types of cancer. Ipilimumab binds to a substance called CTLA-4, which is found on the surface of T cells (a type of white blood cell). Ipilimumab may block CTLA-4 and help the immune system kill cancer cells. It is a type of monoclonal antibody. Also called MDX-010 and Yervoy.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

marker (MAR-ker)

A diagnostic indication that disease may develop.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

medical oncologist (MEH-dih-kul on-KAH-loh-jist)

A doctor who specializes in diagnosing and treating cancer using chemotherapy, hormonal therapy, biological therapy, and targeted therapy. A medical oncologist often is the main health care provider for someone who has cancer. A medical oncologist also gives supportive care and may coordinate treatment given by other specialists.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

melanoma (MEH-luh-NOH-muh)

A form of cancer that begins in melanocytes (cells that make the pigment melanin). It may begin in a mole (skin melanoma), but can also begin in other pigmented tissues, such as in the eye or in the intestines.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

metastatic (meh-tuh-STA-tik)

Having to do with metastasis, which is the spread of cancer from the primary site (place where it started) to other places in the body.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

objective response (ub-JEK-tiv reh-SPONTS)

A measurable response.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

phase I trial (fayz … TRY-ul)

The first step in testing a new treatment in humans. These studies test the best way to give a new treatment (for example, by mouth, intravenous infusion, or injection) and the best dose. The dose is usually increased a little at a time in order to find the highest dose that does not cause harmful side effects. Because little is known about the possible risks and benefits of the treatments being tested, phase I trials usually include only a small number of patients who have not been helped by other treatments.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

phase III trial (fayz … TRY-ul)

A study to compare the results of people taking a new treatment with the results of people taking the standard treatment (for example, which group has better survival rates or fewer side effects). In most cases, studies move into phase III only after a treatment seems to work in phases I and II. Phase III trials may include hundreds of people.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

randomized

Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

reduction (ree-DUK-shun)

A chemical reaction that takes place when a substance comes into contact with hydrogen or another reducing substance.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

regression (reh-GREH-shun)

A decrease in the size of a tumor or in the extent of cancer in the body.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

response (reh-SPONTS)

In medicine, an improvement related to treatment.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

therapy (THAYR-uh-pee)

Treatment.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

tumor (TOO-mer)

An abnormal mass of tissue that results when cells divide more than they should or do not die when they should. Tumors may be benign (not cancer), or malignant (cancer). Also called neoplasm.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

will (wil)

A legal document in which a person states what is to be done with his or her property after death, who is to carry out the terms of the will, and who is to care for any minor children.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)